Novel penten-2-yl-derivatives

ABSTRACT

Novel penten-2-yl derivatives of the formula in the trans form ##STR1## wherein R is selected from the group consisting of hydrogen and acetyl and to a novel process for the preparation of methyl 2,2-dimethyl-3-(2&#39;-methyl-propenyl)-cyclopropane-1,1-dicarboxylate which is an intermediate for chrysanthemic acid.

STATE OF THE ART

Japanese patent application Ser. No. 75-089508 describes the cyclizationof halogenated ethylenic esters in the presence of a base but not apalladium complex.

OBJECTS OF THE INVENTION

It is an object of the invention to provide the novel compounds offormula I and to provide a novel process for their preparation.

It is another object of the invention to provide a novel process for thepreparation of methyl2,2-dimethyl-3-(2'-methyl-propenyl)-cyclopropane-1,1-dicarboxylate.

These and other objects and advantages of the invention will becomeobvious from the following detailed description.

THE INVENTION

The novel compounds of the invention are penten-2-yl derivatives of theformula in the trans form ##STR2## wherein R is selected from the groupconsisting of hydrogen and acetyl. Preferred compounds of formula I aremethyl trans (4-hydroxyl-1,1,4-trimethyl-pent-2-enyl)-propanedioate andmethyl trans (4-acetyloxy-1,1,4-trimethyl-pent-2-enyl)-propanedioate.

The novel process of the invention for the preparation of a compound offormula I comprises reacting a cis compound of the formula ##STR3## withan acetylation agent to obtain a monoacetate of cis form of the formula##STR4## reacting the latter with a sodium malonate derivative of theformula ##STR5## in the presence of a palladium (o) complex in anorganic solvent to obtain a compound of the formula in the trans form##STR6## and optionally reacting the latter with an acetylation agent toobtain a compound of the formula in the trans form ##STR7##

In a preferred mode of the said process, the monoacetylation of thecompounds of formulae II and IA is effected with acetic acid anhydridein the presence of triethylamine and a catalytic amount of4-(N,N-dimethylamino)-pyridine and the palladium (o) complex ispreferably palladium tetrakistriphenyl phosphine. The yields of theprocess are excellent and it begins with a starting material which ischemically simple and inexpensive.

The use of palladium derivatives in the substitution of allylic acetatesis a method only known to be in the case of monofunctional acetates [J.Org. Chem., Vol. 41 (1976), p. 3216]. The advantage of the process ofthe invention essentially resides in the fact that the acetate functionis not removed due to the presence of palladium, the malonate group isregio selectively introduced and that the reaction is stereoselectivepermitting isomerization of the cis form to the desired trans form. Theuse of a palladium derivative which complexes the double bond permitsthe production of only the trans form.

The compounds of formula I are intermediates for the synthesis ofchrysanthemic acid by allowing the production of methyl2,2-dimethyl-3-(2'-methyl-propenyl)-cyclopropane-1,1-dicarboxylate whichhas the formula ##STR8## The said compound is described in Bull. Soc.Chim. Japan, Vol. 50 (10) (1977) p. 2825-2826 and may be reacted withlithium chloride in dimethylsulfoxide in the presence of water asdescribed in J. Org. Chem., Vol. 43 (1978), p. 138 to form thecorresponding methyl monoester which may be epimerized in a strong basesuch as sodium ethylate in ethanol as described in Bull. Soc. Chim. ofFrance, (1966), p. 3499 to obtain methyl trans chrysanthemate which maybe saponified to trans chrysanthemic acid.

The novel process of the invention for the preparation of methyl2,2-dimethyl-3-(2'-methyl-propenyl)-cyclopropane-1,1-dicarboxylatecomprises reacting the compound of formula I wherein R is acetyl with analkali metal hydride in an organic solvent and then with a palladium (o)complex to obtain the said desired compound.

In a preferred embodiment of the said process, sodium hydride in amixture of tetrahydrofuran and hexamethylphosphorotriamide is used andthe reaction mixture is poured into a solution of palladiumtetrakistriphenyl phosphine in a mixture of the same solvents.

The said process may also begin with the compound of formula I wherein Ris hydrogen if in the first step the said compound is acetylated to formthe corresponding monoacetate derivative which is then reacted asbefore.

The interest in the use of a palladium derivative for the cyclizationstep proceeds from the fact that the reaction which is regioselective isaccelerated in the presence of palladium leading in effect under goodconditions by attacking the less blocked pole of the formed complex tothe desired structure.

Finally, the invention permits one to proceed to the trans chrysanthemicstructure, especially methyl trans chrysanthemate in a novel way with areduced number of steps beginning with a readily available hex-2-enederivative.

The compounds of formulae I and V are obtained under perfectlyreproducible conditions with interesting total yields. The compound offormula V is known in the literature and can produce in 2 steps methyltrans chrysanthemate in excellent yields.

The compound of formula II is described in J. Org. Chem. Vol. 27 (1962),p. 2398 and C.A., Vol. 59, p. 2675a and C.A. Vol. 85 (1976), p. 76937 m.

In the following examples there are described several preferredembodiments to illustrate the invention. However, it is to be understoodthat the invention is not intended to be limited to the specificexamples.

EXAMPLE 1 Methyl trans(4-hydroxy-1,1,4-trimethyl-pent-2-enyl)-propane-dioate STEP A: cis2,5-dimethyl-hex-3-ene-2,5-diol

1.6 g of 5% palladized calcium carbonate and 0.6 g of quinoline wereadded to a solution of 24 g of 2,5-dimethyl-hex-3-yne-2,5-diol [Ray etal, Am. Soc., Vol. 74 (1952), p. 1247] in 200 ml of methanol and themixture was stirred with hydrogen until hydrogen absorption ceased. Thecatalyst was removed by filtration and the filtrate was evaporated todryness under reduced pressure to obtain 24.2 g of cis2,5-dimethyl-hex-3-ene-2,5-diol melting at 64° C. which was used as isfor the next step.

STEP B: Monoacetate of cis 2,5-dimethyl-hex-3-ene-2,5-diol

30 ml of triethylamine and 0.840 g of 4-(N,N-dimethylamino)-pyridinewere added to a solution of 10 g of the product of Step A and 10 ml ofmethylene chloride and the mixture was stirred at room temperature for 4hours. 7.1 g of acetic acid anhydride were added thereto followed bymethylene chloride addition. The organic phase was washed with aqueous5% hydrochloric acid and then with water, dried and evaporated todryness under reduced pressure. The 9.6 g of residue werechromatographed over silica gel and were eluted with a 1-25ether-pentane mixture to obtain after distillation 7.8 g of puremonoacetate of cis 2,5-dimethyl-hex-3-ene-2,5-diol with a boiling pointof 60° C. at 0.1 mm Hg.

STEP C: Methyl trans(4-hydroxy-1,1,4-trimethyl-pent-2-enyl)-propanedioate

A solution of the sodium derivative of methyl malonate prepared from0.48 g of sodium hydride as a 50% oil suspension, 1.5 ml of methylmalonate and 15 ml of anhydrous tetrahydrofuran was added at 70° C. to4.86 g of the product of Step B and 0.6 g of palladium tetrakistriphenylphosphine was added thereto. The mixture was stirred at 70° C. for 16hours and was cooled and poured into water. The mixture was extractedwith ether and the organic phase was dried and evaporated to drynessunder reduced pressure. The residue was distilled to obtain 2.2 g ofmethyl trans (4-hydroxy-1,1,4-trimethyl-pent-2-enyl)-propanedioateboiling at 120°-130° C. at 0.01 mm Hg.

EXAMPLE 2 Methyl trans(4-acetyloxy-1,1,4-trimethyl-pent-2-enyl)-propanedioate

2 ml of acetic acid anhydride, 2 ml of triethylamine and 0.084 g of4-(N,N-dimethylamino)-pyridine were added to a solution of 2 g of theproduct of Example 1 in 6 ml of methylene chloride and the mixture wasstirred at room temperature for 6 hours. The methylene chloride phasewas washed with aqueous 5% hydrochloric acid, with an aqueous sodiumbicarbonate solution, then with water, dried and evaporated to drynessunder reduced pressure. The residue was distilled to obtain 1.98 g ofmethyl trans (4-acetyloxy-1,1,4-trimethyl-pent-2-enyl)-propanedioatewith a boiling point of 100°-110° C. at 0.1 mm Hg.

EXAMPLE 3 Methyl2,2-dimethyl-3-(2'-methyl-propenyl)-cyclopropane-1,1-dicarboxylate

A mixture of 0.3 g of the product of Example 2, 0.8 ml oftetrahydrofuran, 0.4 ml of hexamethyltriphosphorotriamide and 0.048 g ofsodium hydride as a 60% oil suspension was stirred at room temperaturefor 30 minutes and then a solution of 0.16 g of palladiumtetrakistriphenyl phosphine, 0.4 ml of hexamethylphosphorotriamide and0.8 ml of tetrahydrofuran was added thereto at 70° C. with stirring over30 minutes. The mixture was stirred for 90 minutes and was poured intowater. The mixture was extracted with ether and the organic phase wasdried and evaporated to dryness. The residue was chromatographed oversilica gel and was eluted with a 1-4 ether-pentane mixture to obtain0.072 g of methyl2,2-dimethyl-3-(2'-methyl-propenyl)-cyclopropane-1,1-dicarboxylate.

Various modifications of the products and processes of the invention maybe made without departing from the spirit or scope thereof and it is tobe understood that the invention is intended to be limited only asdefined in the appended claims.

What is claimed is:
 1. A penten-2-yl derivative of the formula in thetrans form ##STR9## wherein R is selected from the group consisting ofhydrogen and acetyl.
 2. A compound of claim 1 which is methyl trans(4-hydroxy-1,1,4-trimethyl-pent-2-enyl)-propanedioate.
 3. A compound ofclaim 1 which is methyl trans(4-acetyloxy-1,1,4-trimethyl-pent-2-enyl)-propanedioate.